The nature of an ultra-faint galaxy in the cosmic dark ages seen with JWST.

In the first billion years after the Big Bang, sources of ultraviolet (UV) photons are believed to have ionized intergalactic hydrogen, rendering the Universe transparent to UV radiation. Galaxies brighter than the characteristic luminosity L* (refs. 1,2) do not provide enough ionizing photons to drive this cosmic reionization. Fainter galaxies are thought to dominate the photon budget; however, they are surrounded by neutral gas that prevents the escape of the Lyman-α photons, which has been the dominant way to identify them so far. JD1 was previously identified as a triply-imaged galaxy with a magnification factor of 13 provided by the foreground cluster Abell 2744 (ref. 3), and a photometric redshift of z ≈ 10. Here we report the spectroscopic confirmation of this very low luminosity (≈0.05 L*) galaxy at z = 9.79, observed 480 Myr after the Big Bang, by means of the identification of the Lyman break and redward continuum, as well as multiple ≳4σ emission lines, with the Near-InfraRed Spectrograph (NIRSpec) and Near-InfraRed Camera (NIRCam) instruments. The combination of the James Webb Space Telescope (JWST) and gravitational lensing shows that this ultra-faint galaxy (MUV = -17.35)-with a luminosity typical of the sources responsible for cosmic reionization-has a compact (≈150 pc) and complex morphology, low stellar mass (107.19 M⊙) and subsolar (≈0.6 Z⊙) gas-phase metallicity.

A magnified compact galaxy at redshift 9.51 with strong nebular emission lines.

Ultraviolet light from early galaxies is thought to have ionized gas in the intergalactic medium. However, there are few observational constraints on this epoch because of the faintness of those galaxies and the redshift of their optical light into the infrared. We report the observation, in JWST imaging, of a distant galaxy that is magnified by gravitational lensing. JWST spectroscopy of the galaxy, at rest-frame optical wavelengths, detects strong nebular emission lines that are attributable to oxygen and hydrogen. The measured redshift is z = 9.51 ± 0.01, corresponding to 510 million years after the Big Bang. The galaxy has a radius of [Formula: see text] parsecs, which is substantially more compact than galaxies with equivalent luminosity at z ~ 6 to 8, leading to a high star formation rate surface density.

SPINDOC is Highly Expressed in Pan-Cancer Samples and Can Promote the Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating Wnt/ß-Catenin Signaling Pathway.

Purpose: As a novel genetic biomarker, little information is available about the possible role of SPINDOC in different malignant tumors and in hepatocellular carcinoma (HCC). Methods: Based on The Cancer Genome Atlas (TCGA) database, the expression level of SPINDOC in pan-cancer and hepatocellular carcinoma samples was first determined using bioinformatics analysis. The potential relationship between the expression level as well as the clinical characteristics and the molecular mechanisms through which SPINDOC can promote the proliferation, invasion and migration of HCC cells was evaluated. In addition, cell-based studies and in vivo experiments were used to verify the bioinformatics analysis results. Results: Bioinformatics analysis showed that SPINDOC expression was significantly increased in 18 human malignancies and the gene expression level was positively correlated with poor clinical prognosis in kidney renal papillary cell carcinoma (KIRP), pheochromocytoma and paraganglioma (PCPG) and liver hepatocellular carcinoma (LIHC). The main type of genetic variation of SPINDOC was amplification, and the increase of SPINDOC mRNA expression level was directly related to the amplification of this gene. The expression level of SPINDOC in patients with primary HCC was positively correlated with poor clinical prognosis, as well as the clinical grade and stage of carcinoma. Gene set enrichment analysis (GSEA) analysis showed that high expression of SPINDOC could activate Wnt/ß-catenin signaling pathway. Moreover, in vitro and in vivo experiments showed that SPINDOC gene silencing significantly inhibited the proliferation, migration and invasion of Huh7 and SK-HEP-1 cells and decreased the expression of SPIN1, Wnt1, ß-catenin and cyclin D1 but increased the expression of AXIN2. Conclusion: SPINDOC is highly expressed in pan-cancer and HCC samples. This factor can effectively promote the invasion and migration of hepatocellular carcinoma (HCC) cells by activating Wnt/ß-catenin signaling pathway, and thus can serve as a potential therapeutic target for HCC management.

TPL Inhibits the Invasion and Migration of Drug-Resistant Ovarian Cancer by Targeting the PI3K/AKT/NF-κB-Signaling Pathway to Inhibit the Polarization of M2 TAMs.

Chemoresistance is the primary reason for the poor prognosis of patients with ovarian cancer, and the search for a novel drug treatment or adjuvant chemotherapy drug is an urgent need. The tumor microenvironment plays key role in the incidence and development of tumors. As one of the most important components of the tumor microenvironment, M2 tumor-associated macrophages are closely related to tumor migration, invasion, immunosuppressive phenotype and drug resistance. Many studies have confirmed that triptolide (TPL), one of the principal components of Tripterygium wilfordii, possesses broad-spectrum anti-tumor activity. The aims of this study were to determine whether TPL could inhibit the migration and invasion of A2780/DDP cells in vitro and in vivo by inhibiting the polarization of M2 tumor-associated macrophages (TAMs); to explore the mechanism(s) underlying TPL effects; and to investigate the influence of TPL on murine intestinal symbiotic microbiota. In vitro results showed that M2 macrophage supernatant slightly promoted the proliferation, invasion, and migration of A2780/DDP cells, which was reversed by TPL in a dose-dependent manner. Animal experiments showed that TPL, particularly TPL + cisplatin (DDP), significantly reduced the tumor burden, prolonged the life span of mice by inhibiting M2 macrophage polarization, and downregulated the levels of CD31 and CD206 (CD31 is the vascular marker and CD206 is the macrophage marker), the mechanism of which may be related to the inhibition of the PI3K/Akt/NF-κB signaling pathway. High-throughput sequencing results of the intestinal microbiota in nude mice illustrated that Akkermansia and Clostridium were upregulated by DDP and TPL respective. We also found that Lactobacillus and Akkermansia were downregulated by DDP combined with TPL. Our results highlight the importance of M2 TAMs in Epithelial Ovarian Cancer (EOC) migration ability, invasiveness, and resistance to DDP. We also preliminarily explored the mechanism governing the reversal of the polarization of M2 macrophages by TPL.

Antitumor activity of triptolide in SKOV3 cells and SKOV3/DDP in vivo and in vitro.

This study was designed to investigate the antitumor activity of triptolide in ovarian cancer inoculated with SKOV3 and SKOV3/cisplatin (DDP) cells, and to assess the mechanisms. In-vivo and in-vitro experiments were designed to evaluate the effects of triptolide on the tumor growth of SKOV3 and SKOV3/DDP cells. The experiments were divided into four groups: a SKOV3 group, a SKOV3 + TP treatment group, a SKOV3/DDP group and a SKOV3/DDP + TP treatment group. The expression of Sorcin, vascular endothelial growth factor and matrix metalloproteinase-2 were detected by western blotting and immunohistochemistry. Tumor cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. In-vitro experiments showed that compared with SKOV3 control group, the level of colony-stimulating factor 1 and expression of Sorcin in SKOV3/DDP was significantly higher. Interestingly, triptolide treatment could reduce colony-stimulating factor 1 level and expression of Sorcin in both SKOV3 and SKOV3/DDP cell lines. In-vivo experiments showed that tissue necrosis area in SKOV3 + TP and SKOV3/DDP + TP was larger than SKOV3 and SKOV3/DDP group, respectively. Triptolide treatment induced apoptosis in both SKOV3 and SKOV3/DDP cells. Compared with SKOV3 group, the size of tumors was large, and the expression of MMP-2, Sorcin and vascular endothelial growth factor was higher in SKOV3/DDP group. Triptolide treatment reduced the size of tumors, and the expression of MMP-2, Sorcin and vascular endothelial growth factor in SKOV3/DDP as well as in SKOV3 tumors. In conclusion, triptolide has antitumor activity in both SKOV3 and SKOV3/DDP cells likely through inducing apoptosis and regulating MMP-2, Sorcin and vascular endothelial growth factor expression.

Downregulation of SEMA4C Inhibit Epithelial-Mesenchymal Transition (EMT) and the Invasion and Metastasis of Cervical Cancer Cells via Inhibiting Transforming Growth Factor-beta 1 (TGF-ß1)-Induced Hela cells p38 Mitogen-Activated Protein Kinase (MAPK) Activation.

BACKGROUND Epithelial-mesenchymal transition (EMT) plays a key role in promoting invasion and metastasis of tumor cells. SEMA4C can regulate the generation of transforming growth factor-beta 1 (TGF-ß1)-induced EMT in cervical cancer. This study investigated the relationship between the regulation of SEMA4C on TGF-ß1-induced p38 mitogen-activated protein kinase (MAPK) activation and invasion and metastasis of cervical cancer. MATERIAL AND METHODS Hela-shSEMA4C cell line was established and the success of transfection was confirmed with fluorescence intensity. Cell experiments were divided into 2 groups. Group 1 was Hela, Hela-shNC, and Hela-shSEMA4C; and Group 2 was Hela, Hela-shNC, Hela-shSEMA4C, Hela+TGF-ß1, Hela-shNC+TGF-ß1, and Hela-shSEMA4C+TGF-ß1. Group 1 was detected for SEMA4C mRNA expression by real-time polymerase chain reaction (RT-PCR), cell viability by Cell Counting Kit-8 (CCK-8), F-actin fluorescence intensity by immunofluorescence, cell migration by scratch test, and cell invasion by invasion test. Group 2 was analyzed for E-cadherin fluorescence intensity by immunofluorescence, human fibronectin (FN) content by enzyme-linked immunosorbent assay (ELISA), and SEMA4C, E-cadherin and p-p38 expressions by Western blot. RESULTS For Group 1, compared with Hela and Hela-shNC subgroups, the SEMA4C mRNA expression, cell viability, F-actin fluorescence intensity, cell migration and invasion ability in the Hela-shSEMA4C subgroup were significantly decreased (P<0.05). For Group 2, compared with Hela and Hela-shNC subgroups, the E-cadherin expression and fluorescence intensity in the Hela-shSEMA4C subgroup were significantly increased (P<0.01), while the FN content, SEMA4C, and p-p38 MAPK expressions were significantly decreased (P<0.01). Compared with Hela-shNC+TGF-ß1 and Hela+TGF-ß1 subgroups, the E-cadherin expression and fluorescence intensity in the Hela-shSEMA4C+TGF-ß1 subgroup were significantly increased (P<0.01), while the FN content, SEMA4C and p-p38 expressions were significantly decreased (P<0.01). CONCLUSIONS Downregulation of SEMA4C can inhibit EMT and the invasion and metastasis of cervical cancer cells via inhibiting TGF-ß1-induced Hela cells p38 MAPK activation.

Combinatorial Enzymatic Synthesis of Unnatural Long-Chain ß-Branch Pyrones by a Highly Promiscuous Enzyme.

In this study, we described in detail a combinatorial enzymatic synthesis approach to produce a series of unnatural long-chain ß-branch pyrones. We attempted to investigate the catalytic potential of a highly promiscuous enzyme type III PKS to catalyze the non-decarboxylative condensation reaction by two molecules of fatty acyl diketide-N-acetylcysteines (diketide-NACs) units. Two non-natural long-chain (C16, C18) fatty acyl diketide-NACs were prepared successfully for testing the ability of non-decarboxylative condensation. In vitro, 12 novel naturally unavailable long-chain ß-branch pyrones were generated by one-pot formation and characterized by ultraviolet-visible spectroscopy and high-resolution liquid chromatography-mass spectrometry. Interestingly, enzymatic kinetics result displays that this enzyme exhibits the remarkable compatibility to various non-natural long-chain substrates. These results would be useful to deeply understand the catalytic mechanism of this enzyme and further extend the application of enzymatic synthesis of non-natural products.

Association between DAPK1 promoter methylation and cervical cancer: a meta-analysis.

BACKGROUND: Death-associated protein kinase1 (DAPK1) is an important tumor suppressor gene. DNA methylation can inactivate genes, which has often been observed in the carcinogenesis of cervical cancer. During the past several decades, many studies have explored the association between DAPK1 promoter methylation and cervical cancer. However, many studies were limited by the small samples size and the findings were inconsistent among them. Thus, we conducted a meta-analysis to assess the association between DAPK1 promoter methylation and cervical cancer. METHODS: We systematically searched eligible studies in the PubMed, Web of Science, EMBASE and CNKI databases. Using meta-regression, subgroup analysis and sensitivity analysis, we explored the potential sources of heterogeneity. The odds ratio (OR) and 95% confidence interval (95% CI) were calculated by Meta-Analysis in R. RESULTS: A total of 15 studies from 2001 to 2012, comprising 818 tumor tissues samples and 671 normal tissues samples, were analyzed in this meta-analysis. The frequencies of DAPK1 promoter methylation ranged from 30.0% to 78.6% (median, 59.3%) in cervical cancer tissue and 0.0% to 46.7% (median, 7.8%) in normal cervical tissue. The pooled OR was 19.66 (95%CI = 8.72-44.31) with the random effects model, and heterogeneity was found through the sensitivity analysis. The I2 = 60% (P = 0.002) decreased to I2 = 29.2% (P = 0.144) when one heterogeneous study was excluded, and the pooled OR increased to 21.80 (95%CI = 13.44-35.36) with the fixed effects model. CONCLUSION: The results suggested a strong association between DAPK1 promoter methylation and cervical cancer. This study also indicated that DAPK1 promoter methylation may be a biomarker during cervical carcinogenesis that might serve as an early indication of cervical cancer.

Association between RASSF1A promoter methylation and ovarian cancer: a meta-analysis.

BACKGROUND: The RAS association domain family protein 1a gene (RASSF1A) is one of the tumor suppressor genes (TSG). Inactivation of RASSF1A is critical to the pathogenesis of cancer. Aberrant TSG methylation was considered an important epigenetic silencing mechanism in the progression of ovarian cancer. A number of studies have discussed association between RASSF1A promoter methylation and ovarian cancer. However, they were mostly based on a small number of samples and showed inconsist results, Therefore, we conducted a meta-analysis to better identify the association. METHODS: Eligible studies were identified by searching the PubMed, EMBASE, Web of Science, and CNKI databases using a systematic searching strategy. We pooled the odds ratio (ORs) from individual studies using a fixed-effects model. We performed heterogeneity and publication bias analysis simultaneously. RESULTS: Thirteen studies, with 763 ovarian cancer patients and 438 controls were included in the meta-analysis. The frequencies of RASSF1A promoter methylation ranged from 30% to 58% (median is 48%) in the cancer group and 0 to 21% (median is 0) in the control group. The frequencies of RASSF1A promoter methylation in the cancer group were significantly higher than those in the control group. The pooled odds ratio was 11.17 (95% CI = 7.51-16.61) in the cancer group versus the corresponding control group under the fixed-effects model. CONCLUSION: The results suggested that RASSF1A promoter methylation had a strong association with ovarian cancer.

[Expression and clinical significance of Sema4C in esophageal cancer, gastric cancer and rectal cancer].

OBJECTIVE: To explore the expression and clinical significance of signal protein Sema4C in esophageal cancer, gastric cancer and rectal cancer. METHODS: Fifty esophageal cancer, 75 gastric cancer, 50 rectal cancer and 20 corresponding normal mucous membrane specimens, collected during the period of January 2008 to December 2010, were detected with streptavidin-peroxidase immunohistochemistry to detect the expression levels of Sema4C. And the relationships of the Sema4C expression with clinicopathological data was analyzed. RESULTS: The expression levels of Sema4C in three kinds of cancers were significantly higher than the corresponding normal mucous membranes (80.0% (n = 40) vs 20.0% (n = 4), 77.3% (n = 58) vs 25.0% (n = 5), 80.0% (n = 40) vs 15.0% (n = 3), all P = 0.000). Furthermore, the percentage of Sema4C positive cells was significantly higher in carcinoma nests of tumors with lymphatic metastasis than those without (90.3% (n = 28) vs 63.2% (n = 12), 85.0% (n = 51) vs 46.7% (n = 7), 92.0% (n = 23) vs 68.0% (n = 17), P = 0.049, 0.005, 0.034). However, no significant correlations were found between the Sema4C expression with gender, age, location of tumors, types of cancer cells, cell differentiation, tumor size, depth of invasion or tumor stage (all P > 0.05). CONCLUSION: There is a high expression of Sema4C in esophageal cancer, gastric cancer and rectal cancer. And it is strongly correlated with lymphatic metastasis. Thus Sema4C may play critical roles in the invasion and lymphatic metastasis of esophageal cancer, gastric cancer and rectal cancer.